Jenkins and Peters have postulated that a decreased activity of the cytosolic form of aldehyde dehydrogenase (ALDH1) is an important marker for the development of alcoholic liver disease. While this hypothesis is provocative and potentially important, it has not been supported by findings from other laboratories or by subsequent results from the same research group. Additionally, the finding of decreased cytosolic ALDH is questionable because a body of evidence now indicates that it is the mitochondrial ALDH (ALDH2), not cytosolic ALDH (ALDH1), that plays the critical role in regulating acetaldehyde metabolism. Preliminary immunological studies from our laboratory support the idea that the relative ratio of ALDH2/ALDH1 in liver is decreased in alcoholic liver disease. In this pilot project, we wish to extend our preliminary data to show that: (1) it is the mitochondrial ALDH2 and not the cytosolic ALDH1 that is preferentially decreased by alcohol-induced injury. (2) Regenerating nodules in cirrhosis, whether alcoholic or non-alcoholic, are characterized by low ALDH2/ALDH1 ratio. We believe that the use of immunochemical analysis of ALDH1 and ALDH2 and the judicious choice of multiple reference units to express enzyme contents and activities in liver, as proposed here, should clarify the controversy. If the results from this study indicate that ALDH2 is preferentially affected by alcoholic liver disease, we will test whether this process is specific for this enzyme or nonspecific, i.e. reflecting general mitochondrial injury.